Clinical predictors of ACE-inhibitor induced dry cough in 27492 patients with cardiovascular disease using individual data of randomized clinical trials

Abstract

Purpose: To investigate the incidence and clinical predictors of dry cough in patients treated with ACE-inhibitors. Dry cough is a frequent reason to stop ACE-inhibitor treatment. Methods: We studied 27.492 ACE-inhibitor naive patients randomized to ACE-inhibitor or placebo for the incidence of dry cough using individual data of 3 large randomized placebo controlled trials (EUROPA, PROGRESS and ADVANCE). Multivariate regression analysis was used to study the incidence of cough in relation to baseline clinical characteristics including racial background. Results: In 27.492 patients with cardiovascular disease, 1076 patients discontinued ACE-inhibitor treatment due to cough (3.9%), 703 patients during run-in period of 4 weeks (2.6%, short-term cough) and 373 patients during a mean follow-up of four years (3.1%, long-term cough). During follow-up, 96 patients experienced cough in the placebo group (0.8%). Significant determinants of cough were female gender (OR 1.92 95% CI 1.68-2.18); age above 65 years (OR 1.53 95% CI 1.35-1.73) and statin use (OR 1.37; 95% CI 1.18-1.59). A clinical risk score composed of these 3 predictors of cough is shown in figure 1, the highest risk score 3 mounted to an odds ratio of 4.4 (95% CI 3.1-5.4). Racial background was not related to a differential incidence of cough in Caucasian or Asian descendent patients (OR 1.11 95% CI 0.92-1.39). No difference was found in determinants of short-term versus long-term ACE-inhibitor related cough. ![Figure][1] Figure 1 Conclusion: This large analysis of 3 clinical trials in 27.492 patients shows an overall lower incidence of ACE-inhibitor induced cough (3.9%) as compared to literature. The highest incidence of cough was seen especially in female patients at older age. In contrast, racial differences were not related to the incidence of dry cough. [1]: pending:yes